This proposal presents new approach to combating chemical hazards of the industrial and urban environment. Our goal is to demonstrate the possible therapeutic use of zinc and certain chelating agents in the prevention of tissue injury caused by toxic metals and gases. A new concept of the biological action of zinc, based on our recent findings, is proposed suggesting that the membrane stabilizing effect of Zn or the Zn:8-HQ complex is related either to an interference with metal-catalyzed lipid peroxidation and oxidation of thiol groups of the membrane components or to the formation of stable mercaptides with thiol groups. However, other possible mechanisms of the effect of zinc will also be explored. This working hypothesis will be tested by the following experiments: The development of lung edema in mice exposed to NO2 will be pursued further to uncover the molecular mechanism of the protective action of zinc. The effect of Zn and Zn:8-HQ on the toxicity of selected metals of toxicological interest (Cu, Cd, Pb, Ni, Be) will be evaluated in in vivo experiments using models of acute and chronic lung edema in the mouse and of renal injury in the rat. The finding that in biological systems zinc protects against the toxic effect of copper or cadmium will be explored further. The function of lung macrophages (phagocytosis and viability) and dog lymphocytes (microcytotoxicity) affected by various toxic agents will be studied after similar treatment. The lysosomal and mitochondrial membrane as well as macromolecular lipoprotein models of biological membranes will be used for further investigation of the interaction of zinc and other metals with membrane components. All proposed studies will be performed with close cooperation of a biologist, biochemist, pathologist, and clinically-oriented physician.